Phase II Open-Label, Multi-Center, Prospective, Randomized Study of LCP-Tacro vs. Azathioprine for the Treatment of Autoimmune Hepatitis - Full Text View

Sponsored by:	LifeCycle Pharma A/S
Information provided by:	LifeCycle Pharma A/S
ClinicalTrials.gov Identifier:	NCT00608894

Purpose

An open-label, multi-center, prospective, randomized study to evaluate the efficacy, safety and tolerability of LCP-Tacro tablets given once daily vs. azathioprine, each in combination with prednisone, for the treatment of autoimmune hepatitis (AIH).

Condition	Intervention	Phase
Autoimmune Hepatitis	Drug: LCP-Tacro + prednisone Drug: Azathioprine + prednisone	Phase II

MedlinePlus related topics: Hepatitis

Drug Information available for: Prednisone Tacrolimus Corticosteroids Tacrolimus anhydrous Azathioprine Azathioprine sodium salt Benzocaine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II, Open-Label, Multi-Center, Prospective, Randomized Study of LCP-Tacro Tablets vs. Azathioprine, in Combination With Corticosteroids, for the Treatment of Autoimmune Hepatitis

Further study details as provided by LifeCycle Pharma A/S:

Primary Outcome Measures:

Percent of patients that achieve biochemical remission of (AIH) at Month 6 during treatment with LCP-Tacro + prednisone or azathioprine + prednisone. Biochemical remission is defined as ALT, total bilirubin and gamma globulin within normal limits. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent of patients who achieve biochemical remission by Month 3 during treatment with LCP-Tacro + prednisone or azathioprine + prednisone. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Percents of patients in each treatment group classified as either in remission, having an incomplete response, a treatment failure, or a case of relapse. Each patient will be classified as being one of the four states at Month 6. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	December 2007
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental LCP-Tacro + prednisone	Drug: LCP-Tacro + prednisone LCP-Tacro tablets starting at 2 mg once daily, then adjusted to achieve and maintain target whole blood tacrolimus levels of 3 - 6 ng/mL, plus prednisone 30 mg/day for one week, then 20 mg/day for one week, then 15 mg/day for two weeks, then 10 mg/day through Month 6.
2: Active Comparator Azathioprine + prednisone	Drug: Azathioprine + prednisone Azathioprine tablets 50 - 100 mg (approximately 1 mg/kg) once daily, plus prednisone 30 mg/day for one week, then 20 mg/day for one week, then 15 mg/day for two weeks, then 10 mg/day through Month 6.

Detailed Description:

An open-label, multi-center, prospective, randomized study to evaluate the efficacy, safety and tolerability of LCP-Tacro tablets given once daily vs. azathioprine for the treatment of autoimmune hepatitis (AIH).

Patients with histologically confirmed chronic hepatitis who fulfill criteria established by the International Autoimmune Hepatitis Group (IAIHG) and Inclusion and Exclusion criteria will be enrolled after having signed an informed consent document.

Up to 60 patients will be randomized (1:1) to receive treatment with LCP-Tacro + prednisone vs. azathioprine (AZA) + prednisone.

LCP-Tacro will be started at 2 mg once daily (q.d.) with weekly measurement of tacrolimus whole blood trough levels and adjustment of the daily dose of LCP-Tacro to achieve target tacrolimus levels of 3 - 6 ng/mL. Patients with histological evidence of cirrhosis and a Model for End-Stage Liver Disease (MELD) score ≤ 8 will commence LCP-Tacro at a fixed dose of 1 mg once daily, with subsequent dosage adjustments to maintain tacrolimus trough levels at 3 - 6 ng/mL.
AZA will be started at 50 - 100 mg (approximately 1 mg/kg) once daily (q.d.).

Patients will also commence treatment with prednisone 30 mg/day for one week, then 20 mg/day for one week, then 15 mg/day for two weeks, then 10 mg/day through Month 6.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men and women at least 18 years of age with a diagnosis of definite or probable AIH defined by the revised International Autoimmune Hepatitis Group (IAIHG) criteria
Elevation of serum ALT ≥ 1.5 times the upper limit of normal
Liver biopsy showing chronic hepatitis consistent with AIH
Patients able to swallow the study medication
Patients capable of understanding the purposes and risks of the study, who can give written informed consent and who are willing to participate in and comply with the study
Women of childbearing potential must have a negative serum pregnancy test within seven days prior to receiving study medication and agree to use contraceptive measures to avoid pregnancy during participation in the trial.

Exclusion Criteria:

Patients with other concurrent liver disease
Patients with cirrhosis on liver biopsy with a MELD score > 15
Patients with a history or presence of decompensated liver disease
Patients with serum creatinine ≥ 1.5 mg/dL prior to enrollment
Patients positive for HCV RNA or Hepatitis B surface antigen (HBsAg)
Patients with a history of alcohol intake > 25 g/day within the past six months
Patients with TSH outside normal range accompanied by an abnormal T4
Patients with alpha-fetoprotein ≥ 20 ng/mL
Patients with severe anemia (hemoglobin < 8 g/dL), leukopenia (WBC < 4000/mm3), or thrombocytopenia (platelet count < 100,000/mm3)
Patients with a history of recent exposure to hepatotoxic drugs
Patients who require therapy with any immunosuppressive agent other than those prescribed in the study
Patients unable or unwilling to provide informed consent
Pregnant or nursing women
Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception
Patients who have been treated with another investigational agent in the three months prior to enrollment
Patients receiving any drug interfering with tacrolimus metabolism
Patients with current malignancy or a history of malignancy (within the past 5 years), except basal or non-metastatic squamous cell carcinoma of the skin that has been treated successfully
Patients with uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives
Patients with severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of tacrolimus
Patients with a known hypersensitivity to azathioprine, corticosteroids or tacrolimus
Patients with any form of current substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator
Patients who are recipients of an organ transplant or who require treatment with immunosuppressives or corticosteroids for any disease other than AIH.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608894

Locations

United States, Arizona
Mayo Clinic - Phoenix
Phoenix, Arizona, United States, 85054
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32216
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Texas
St. Luke's Advanced Liver Therapies
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Canada, Alberta
Zeildler Ledcor Centre
Edmonton, Alberta, Canada, T6G 2X8
Heritage Medical Research Clinic
Calgary, Alberta, Canada, T2N 4N1
Canada, Manitoba
John Buhler Research Centre, University of Manitoba Health Sciences Centre
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 2Y9

Sponsors and Collaborators

LifeCycle Pharma A/S

Investigators

Principal Investigator:	Gerald Y Minuk, M.D.	University of Manitoba Health Sciences Centre, Winnipeg
Principal Investigator:	Andrew Mason, MD	University of Alberta, Edmonton
Principal Investigator:	Russell H Wiesner, MD	Mayo Clinic - Rochester, MN
Principal Investigator:	John M Vierling, MD	Baylor College of Medicine
Principal Investigator:	Velimir A Luketic, MD	Virginia Commonwealth University, Richmond, VA
Principal Investigator:	Joseph A Odin, MD, PhD	Mount Sinai Medical Center, New York, NY
Principal Investigator:	Elizabeth Carey, MD	Mayo Clinic - Phoenix
Principal Investigator:	John R Lake, MD	University of Minnesota
Principal Investigator:	Barry G Rosser, MD	Mayo Clinic
Principal Investigator:	Steven L Flamm, MD	Northwestern University
Principal Investigator:	Kevork M Peltekian, MD	Queen Elizabeth II Health Sciences Centre
Principal Investigator:	Mark G Swain, MD	University of Calgary

More Information

Responsible Party:	LifeCycle Pharma A/S ( Lawrence Chodoff, Pharm.D. )
Study ID Numbers:	LCP-Tacro Study 2016, Not applicable.
Study First Received:	January 23, 2008
Last Updated:	June 23, 2008
ClinicalTrials.gov Identifier:	NCT00608894
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada

Keywords provided by LifeCycle Pharma A/S:

Autoimmune hepatitis
Chronic active hepatitis

Study placed in the following topic categories:

Hepatitis
Prednisone
Liver Diseases
Azathioprine
Autoimmune Diseases
Digestive System Diseases

Hepatitis, Chronic
Benzocaine
Tacrolimus
Autoimmune hepatitis
Hepatitis, Autoimmune

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents, Hormonal
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents

Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunosuppressive Agents
Glucocorticoids
Hormones
Pharmacologic Actions
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on January 16, 2009